10-119115358-G-C

Variant names:

• chr10-119115358-G-C
• rs11198783
• NM_207009.4:c.333-2161G>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_207009.4(DENND10):​c.333-2161G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 138,046 control chromosomes in the GnomAD database, including 21,448 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.54 (21448 hom., cov: 22)
• Consequence: DENND10 NM_207009.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0740
• Publications: 7 publications found

Genes affected

DENND10 (HGNC:31793): (DENN domain containing 10) Enables guanyl-nucleotide exchange factor activity and small GTPase binding activity. Involved in endosome transport via multivesicular body sorting pathway; protein transport; and regulation of early endosome to late endosome transport. Located in late endosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BS2: High Homozygotes in GnomAd4 at 21448 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207009.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DENND10	NM_207009.4	MANE Select	c.333-2161G>C		intron	N/A	NP_996892.1
	DENND10	NM_001303111.2		c.309-2161G>C		intron	N/A	NP_001290040.1
	DENND10	NM_001303112.2		c.114-2161G>C		intron	N/A	NP_001290041.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DENND10	ENST00000361432.3	TSL:1 MANE Select	c.333-2161G>C		intron	N/A	ENSP00000354688.2
	DENND10	ENST00000648560.1		c.-1-2161G>C		intron	N/A	ENSP00000496780.1
	DENND10	ENST00000448258.6	TSL:3	n.299-2161G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.542 AC: 74766 AN: 137942 Hom.: 21440 Cov.: 22

Gnomad AFR AF: 0.421

Gnomad AMI AF: 0.680

Gnomad AMR AF: 0.580

Gnomad ASJ AF: 0.643

Gnomad EAS AF: 0.620

Gnomad SAS AF: 0.671

Gnomad FIN AF: 0.525

Gnomad MID AF: 0.685

Gnomad NFE AF: 0.585

Gnomad OTH AF: 0.587

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.542 AC: 74804 AN: 138046 Hom.: 21448 Cov.: 22 AF XY: 0.541 AC XY: 35752 AN XY: 66122

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.421 AC: 15954 AN: 37918

American (AMR) AF: 0.580 AC: 7467 AN: 12884

Ashkenazi Jewish (ASJ) AF: 0.643 AC: 2119 AN: 3294

East Asian (EAS) AF: 0.621 AC: 2915 AN: 4696

South Asian (SAS) AF: 0.671 AC: 2890 AN: 4304

European-Finnish (FIN) AF: 0.525 AC: 4108 AN: 7820

Middle Eastern (MID) AF: 0.673 AC: 187 AN: 278

European-Non Finnish (NFE) AF: 0.584 AC: 37474 AN: 64114

Other (OTH) AF: 0.589 AC: 1116 AN: 1894

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.413 Hom.: 1099

Bravo AF: 0.549

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.4
DANN	Benign	0.52
PhyloP100		-0.074
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11198783; hg19: chr10-120874870;